US9034866, 129

ID: ALA4073390

PubChem CID: 89759863

Max Phase: Preclinical

Molecular Formula: C22H19FN4O3

Molecular Weight: 406.42

Molecule Type: Small molecule

Names and Identifiers

Canonical SMILES:  Cc1cc([C@](C)(O)C#Cc2cc3c(cc2F)C2CC(C2)n2cc(C(N)=O)nc2-3)no1

Standard InChI:  InChI=1S/C22H19FN4O3/c1-11-5-19(26-30-11)22(2,29)4-3-12-8-16-15(9-17(12)23)13-6-14(7-13)27-10-18(20(24)28)25-21(16)27/h5,8-10,13-14,29H,6-7H2,1-2H3,(H2,24,28)/t13?,14?,22-/m1/s1

Standard InChI Key:  OHSPVJFJVRIKGA-DVUMAKGASA-N

Molfile:  

     RDKit          2D

 30 34  0  0  1  0  0  0  0  0999 V2000
   11.0022   -5.4466    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.0980   -4.6576    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.6358   -4.9923    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.8657   -3.7051    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.8567   -2.5963    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   10.2315   -3.1636    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.5218   -1.1333    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.4012   -0.3168    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.2546    0.0366    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    7.0877   -0.6910    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.6535   -0.2486    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2194    0.1938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1198   -0.8265    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.6852   -0.3846    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3514    1.0778    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.4522    2.0983    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.8856    1.6562    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.7653    2.4724    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000    1.7286    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0934   -0.0745    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.6852   -0.3847    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.3515    1.0777    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.7500   -1.5574    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
   -1.2135   -2.9844    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0000   -3.8661    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2135   -2.9844    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    0.7500   -1.5574    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0031   -5.3643    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.0432   -5.9628    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
   -1.0350   -5.9661    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  1  0
  4  5  2  0
  5  6  1  0
  6  2  2  0
  5  7  1  0
  7  8  1  6
  7  9  1  0
  7 10  1  0
 10 11  3  0
 11 12  1  0
 12 13  2  0
 13 14  1  0
 14 15  2  0
 15 16  1  0
 16 17  2  0
 17 12  1  0
 17 18  1  0
 15 19  1  0
 19 20  1  0
 20 21  1  0
 21 22  1  0
 22 19  1  0
 21 23  1  0
 23 24  1  0
 24 25  2  0
 25 26  1  0
 26 27  2  0
 27 14  1  0
 27 23  1  0
 25 28  1  0
 28 29  2  0
 28 30  1  0
M  END

Alternative Forms

1. Parent:

   

   ALA4073390

   9-fluoro-10-[(3R)-3-hydroxy-3-(5-methyl-1,2-oxazol-3-yl)but-1-ynyl]-5,6,7,12-tetrahydro-5,7-methanobenzo[c]imidazo[1,2-a]azepine-2-carboxamide

Molecule Features

Natural Product: No

Oral: No

Chemical Probe: No

Parenteral: No

Molecule Type: Small molecule

Topical: No

First In Class: No

Black Box: No

Chirality: No

Availability: No

Prodrug: No

Calculated Properties

Molecular Weight: 406.42

Molecular Weight (Monoisotopic): 406.1441

AlogP: 2.78

#Rotatable Bonds: 2

Polar Surface Area: 107.17

Molecular Species: NEUTRAL

HBA: 6

HBD: 2

#RO5 Violations: ┄

HBA (Lipinski): 7

HBD (Lipinski): 3

#RO5 Violations (Lipinski): ┄

CX Acidic pKa: 11.64

CX Basic pKa: 2.69

CX LogP: 2.56

CX LogD: 2.56

Aromatic Rings: 3

Heavy Atoms: 30

QED Weighted: 0.64

Np Likeness Score: -0.66

References

1.  (2015)  Tricyclic compounds and methods of use therefor, 

2. Castanedo GM, Blaquiere N, Beresini M, Bravo B, Brightbill H, Chen J, Cui HF, Eigenbrot C, Everett C, Feng J, Godemann R, Gogol E, Hymowitz S, Johnson A, Kayagaki N, Kohli PB, Knüppel K, Kraemer J, Krüger S, Loke P, McEwan P, Montalbetti C, Roberts DA, Smith M, Steinbacher S, Sujatha-Bhaskar S, Takahashi R, Wang X, Wu LC, Zhang Y, Staben ST..  (2017)  Structure-Based Design of Tricyclic NF-κB Inducing Kinase (NIK) Inhibitors That Have High Selectivity over Phosphoinositide-3-kinase (PI3K).,  60  (2): [PMID:28005357] [10.1021/acs.jmedchem.6b01363]

3. Feng JA, Lee P, Alaoui MH, Barrett K, Castanedo G, Godemann R, McEwan P, Wang X, Wu P, Zhang Y, Harris SF, Staben ST..  (2019)  Structure Based Design of Potent Selective Inhibitors of Protein Kinase D1 (PKD1).,  10  (9): [PMID:31531194] [10.1021/acsmedchemlett.8b00658]

4. Song J,Zhu Y,Zu W,Duan C,Xu J,Jiang F,Wang X,Li S,Liu C,Gao Q,Li H,Zhang Y,Tang W,Lu T,Chen Y.  (2021)  The discovery of quinoline derivatives, as NF-κB inducing kinase (NIK) inhibitors with anti-inflammatory effects in vitro, low toxicities against T cell growth.,  29  [PMID:33199201] [10.1016/j.bmc.2020.115856]

Source

Source(2):

• Scientific Literature
• BindingDB Database